Preparation of hydroxy cyclammonium quaternary salts



Patented Feb. 13, 1 951 UNITED STATES PATENT OFFICE PREPARATION OF HYDROXY CYCLAM- MONIUM QUATERNARY SALTS Earl J. Van Lare and Leslie G. S. Brooker, Rochester. N. Y., assignors to Eastman Kodak Company, Rochester, N. Y., a corporation of New Jersey No Drawing. Application April 3, 1948, Serial N0. 18,845

6 Claims.

yields of hydroxy cyanine dyes prepared from,

hydroxy cyclammonium quaternary salts which are prepared by heating a hydroxy heterocyclic nitrogen base with an alkyl salt, are minimal.

-Kiprianov, Ushenko and Sych, J. Gen. Chem. U; S. S. R. 15, 200-206 (1945) showed that G-methoxy-Z-methylbenzothiazole could be hydrolyzed with concentrated hydrobromic or hydrochloric acid to give (i-hydroxy-Z-methylbenzothiazole hydrobromide or hydrochloride. They showed that when 6-methoxy-2-methylbenzothiazole ethobromide was hydrolyzed with hydrobromic acid, not only was the methoxyl group hydrolyzed, but splitting out of alkyl halide took place, so that the 6-hydroxy-2-methylbenzothiazole quaternary salt could not be obtained by such method. To obtain the quaternary salt of 6-hydroxy-2-methylbenzothiazole,

Kiprianov et a1. were forced to resort to treating the hydrochloride of G-hydroxy-Z-methylbenzothiazole with ethyl p-toluenesulfonate which tends to contaminate the hydroxy quaternary salt owing to methylation of the hydroxyl group, as. discussed above in connection with heating 6-hydroXy-2-methylbenzothiazole with dimethyl sulfate to form the quaternary salt.

We have now found that unlike the ethobromide of 6-methoxy-2-methylbenzothiazole, the ethiodide and other alkiodides of S-methoxy-2-methylbenzothiazole can be hydrolyzed, in hydrobromic acid, to give the G-hydroxy-Z- methylbenzothiazole quaternary salt, without the splitting out of alkyl halide. Thus, pure 6-hydroxy-Z methylbenzothiazole quaternary salts free. from contaminating alkoxyl derivatives can be-obtained. Not only can 6-methoxy-2-methylbenzothiazole alkiodides be so hydrolyzed, but other a1koxy-2-methylbenzothiazole alkiodides and alkoxy-Z-methylbenzoxazole alkiodides be so hydrolyzed to give pure hydroxy-Z-methylbenzo- I thiazole and 2 hydroxy methylbenzoxazole quaternary salts. The alkobromide is obtained as the hydrolysis product and this can be con verted to the alkiodide which, in turn, can be con-' verted to the alkochloride.

It is, accordingly, an object of our invention to provide new hydroxy cyclammonium alkohalidesm A further object is to provide a process for pre-' paring hydroxy cyclammonium quaternary salts free from contaminating alkoxy cyclammonium quaternary salts. A still further object is to pro-' vide new hydroxy dyes free from contaminating alkoxy dyes. Still further objects will become apparent hereinafter.

In accordance with our inventionywe provide hydroxy cyclammonium quaternary salts which are free from contaminating alkoxy cyclammom'um quaternary salts by hydrolyzing, in hydrobromic acid, an alkoxy oyclammonium alkiodide selected from those represented by the following general formula:

wherein Q represents an atom selected from-the group consisting of an oxygen atom, a sulfur atom and a selenium atom, R represents an alkyl group, e. g. methyl, ethyl, n propyl, isopropyl,- n-butyl, isobutyl, etc., and R1 represents an alkyl.

group, especially a primary alkyl group, e. g.

methyl, ethyl, n-propyl, n-butyl, isobutyl, etc.

The hydrobromic acid employed advantageous ly contains from 35 to 48 per cent by weight of hydrogen bromide, the remainder, of course, being water. Constant boiling hydrobromic acid, i. e. the 48 per cent, is most advantageously employed. The hydrolysis is carried out most advantageously by refluxing the mixture of hydrobromic acid and alkoxy cyclammonium alkiodide. However, higher or lower temperatures can be used, e. g. temperatures from to C.

The hydrolysis product is a hydroxy cyclam monium alkobromide and this is advantageously converted to the hydroxy cyclammom'um alkiodide by treating a solution of the hydrolysis prod-@' not with an aqueous or alcoholic solution of a water-soluble metal iodide, e. g. an alkali metalj iodide, e. g. sodium or potassium iodide. The hydroxy cyclammonium .alkiodide can be converted to the hydroxy cyclammonium alkochlo-r ride by heating the hydroxy cyclammonium .allt.

iodide with a suspension of silver chloride in methyl alcohol, or with a suspension of silver chloride in a phenol, according to the process described in United States Patent 2,245,249, dated June 10, i941. The alkobromide can be regenerated from the alk'o'chloride by treating a so lution of the alkochloride with a concentrated aqueous solution of sodium or potassium bro= The following examples will serv illustrate further the manner of practicing our intention.

Example 1.--5-hydroa:y-2-methyiben2omazoie methiodide refluxed for three hours with 75 cc. 4!; per cent hydrobromic acid. "Ifh e brown solution was chilled and the solid which separated was filtered oiff'. ,It was dissolved in 200 cc. of ethyl alcohol and to the hot solution was added a solution of 33.8 g. sodium iodide in a minimum of ethyl alcohol. The resulting solution was cooled, the solid was filtered ofi. It was washed with a small amount of cold ethyl alcohol and dried. rA yield of. 35.'2.:g., '74 per cent, was obtained. Melting point'257- 60" C. with decomposition-tan crystals.

. Example 2.-6 hydroxy-z-mthiiilaenzotfiidzdl methiodide 21.7 g. of eethoxy-z uieth i benzothiazole methiodide and 34 cc. of 48 percent hydrobromic acid were mixed in a 200 cc. flask and refluxed 2 hours. The solution was chilled to 0 C. and filtered. The solid was washed with a small amo n P a n t, w s. d ssel d me yl e c: b1 and treated in the hotwithja solutio'i jo'i' 4 grams of colorless solid was obtained of melting point 275 C. with decomposition.

Example 4.-5-hydro:cy-Z-methylbenzothiazole methiodide c-cm Q ed. 1

22.5 grams of 5 inethoxy-2-methylbenzothiaiol' methiodide were dissolved in 35 cc. of 48 per cent hydrobroinic acid and the solution was refluxed l /2 hours. The clear solution was chilled in iarefrig'erator whereupon solid separated. The solid was filtered off and dissolved in ethyl alcohol. The solution was treated with a saturated hot solution of 13.5 grams of sodium iodide (1 mol. -jpercent excess) in ethyl alcohol. The

- so ution was Chilld and the 'solidfilt'ere or:

335 grams of 6 methoxy z methyibenzotht azole 'ethiodi'de andco. "of '48 percent hydrobromic 'acid were mixed in a 200 cc. flask andre fiuxed 1 'hours. The reaction mixture was chilled to '0 C. and the separated solid'was filtered as dry as possible. The-solid was dissolved ii'l900 cc. of methyl'alcohol andtratedwith a .solution'of 15 grams of sodiumiodide in 1006C.

ot'inethyl alcohol. The solutionWasjchilledto 0 :C.-, the separated solid was filtered "off an 'd washed with methyl alcohol. '18. "ylld "Of 2017 and washed with a srfiall amount of ethyl alco ol. A, yield of 13.4 grams, 62 per cent, was "I 4 taiiied of inelting sonnets-6 c. with decomposition.

fificaihple 5.'5-hydroaiy-2emethfllbeizeothiceole ethiodid selena zole ethiodide, etc.

Th'e a1koxy "Cyclamen-mama quaternary sans employed our new processcan be prepardb'y heating the corr sponding *alk'oxy 'het-oro'cyclic nitrogen base with the 'alkyl'iodide; erg. methyl iodide, etny iodide, nqoropyl 'iodi'd'e', 'n but yl iodide, *i'sobutyl iodide, "etc. 'usi'n'g i a closed 'tulsie fortheheatin'g where higher teinperatuies are desired for volatility of the reactants deihar-id's. alkoxy eter'oeyelie nitro en eases -t em selves, fioin'which 'the"alkio'dide's canoe s .5"? pared, "are known for *the most part, The a1...

5. koxymethylbenzothiazole bases can be prepared by the method of Fries et al., Ann. 407, 208 (1915) in which the appropriate thioacetylalkoxyaniline is oxidized with alkaline potassium ferricyanide. Thus p-methoxyaniline (p-anisidine) gives G-methoxy-Z-methylbenzothiazole. The thioacetylalkoxyanilines can be.prepared by treating the corresponding acetylalkoxyaniline with phosphorus pentasulfide. The acetylalkoxyanilines can be prepared by the action of acetic anhydride or acetyl chloride on the corresponding alkoxyaniline compound. Several of the alkoxy-Z-methylbenzothiazole bases can also be prepared by reducing ('o-nitrophenyl) disulfides with zinc dust and acetic acid, acetylating the reduction mixture with acetic anhydride and closing the ring by heating the resulting mixture. The bis (o-nitrophenyD-disulfides can be prepared from the corresponding l-bromo-Z-nitroalkoxybenzenes by heating the 1-bromo-2-nitroalkoxyhenzene with sodium disulfide in methyl alcohol. Thus 2-bromo-5-methoxynitrobenzene gives his (a-inethoxy-2-nitrophenyl)disulfide which, on reduction and acetylation of the reduction product and closing the ring by heating the resulting mixture, gives 5-methoxy-2-methylbenzothiazole.

The alkoxy-2-methylbenzoxazoles can be prepared by treating the appropriate alkoxy-o aminophenol with an excess of ac-tic anhydride, distilling off the acetic acid generated in the reaction as it is formed. Thus Z-hydroxyA-methoxyaniline and acetic anhydride gives 6-methoXy-2- methylbenzoxazole, etc.

The alkoxy-Z-methylbenzoselenazole bases can be prepared by reducing (o-nitroph-nyl)diselenides with zinc dust and acetic acid, acetylating the reduction mixture with acetic anhydride and closing the ring by heating the resulting mixture. The 'bis (o-nitrophenyl)diselenidcs can be prepared from the corresponding l-bromo-Z-nitroalkoxybenzenes by heating the 1bromo-2-nitroalkoxybenzenes with sodium diselenide in methyl alcohol. Thus, Z-bromo-5-methoxynitrobenzene gives bis i-methoxy-Z-nitrophenyl)diselenide which, on reduction and acetylation of the re' duction product and closing the ring by heatingthe resulting mixture, gives 5-methoXy-2-methy1- benzcselenazole. See also Clark, J. Chem. Soc.

(London), 1928, 2313, for the general method.

The hydroxy cyclammonium alkohalides of our invention can be employ-d to prepare cyanin'e,

styryl and merocyanine dyes. Thus, the hydroxy cyclammonium alkohalides can be condens dwith cyclammonium allryl quaternary salts containing an iodine atom or a thioether group in a reactive position (i. e. the aor y position) to give monomethine cyanine dyes containing a hydroxyl group. The condensations are advantageously effected in the presence of a basic condensing agent, e. g. a tertiary amine e. g. a trialkylamine, such as triethylamine, tri-n-propylmine, triisoamylamine, N-methylpiperidine, N-ethylpiperidine, etc. Typical cyclammonium alkyl quaternary salts containing an iodine atom or thioether group are: Z-iodoquinolin ethiodide, 2-iodoquinoline n-butiodi-de, 2-methylmercaptobenzothiazole metho-p-toluenesulfonate, Z-methylbenzoxazole etho-p-toluenesulfonate, 2-methy1mercapto-B-naphthothiazole etho-p-toluenesulfonate, etc.

The hydroxy cyclammonium alkohalides can be condensed with alkyl orthocarboxylates, e. g. ethyl orthoformate, ethyl orthoacetate, ethyl orthopropionate, methylcrthoformate, etc., in pyle idine, to give symmetrical carbocyanine dyes.

The hydroxy cyclammonium alkohalides' can be condensed with cyclammoniurn quaternary salts containing, in a reactive position, a ,8,-aryl-.

aminovinyl or a fl-acylated arylaminovinyl group to give unsymmetrical carbocyanine dyes. condensations are advantageously effected :in the presenceof a basic condensing agent, e. g. the tertiary amines set forth above. Typical cyclam-' monium quaternary salts containing a p-arylaminovinyl or fi-acylated arylaminovinyl group are: B-acetanilidovinylbenzoxazole ethiodide, fi

anilinovinylthiazoline methiodide, p-acetanilidovinylbenzothiazole ethiodide, 4- (B-anilinovinyl) n-butiodide, 2- [2- (N-methylanilino) quinoline vinyllbenzothiazole ethiodide, 2-B-acetani1idovinyl-4-methylthiazo1e ethiodide, etc.

The hydroxycyclammonium alkohalides can be condensed with ,e-anilinoacrolein anil hydrochloride or with glutaconic dianilide hydrochloride, in'

the presence of a basic condensing agent, e. g. a

tertiary amine, e. g. those set forth above, to give diand tricarbocyanine dyes.

The hydroxy cyclammonium alliohalides can be condensed with heterocyclic compounds containing a ketomethylene group (CH2-CO) and alkyl orthocarboxylates, e. g. ethyl orthoformate,

ethyl orthoacetate, ethyl orthopropionate, etc., in, the presence of pyridine, to give mercarbocyanine' dyes. Typical ketomethylene compounds include rhodanine, S-ethylrhodanine, B-fi hydro yethyL- rhodanine, 3-phenylrhodanine, 3-ethyl-2-thio-2A-- (3,5) -0xazoledione, 1-methyl-3-phenyl-5-pyrazolone, 3-;8-carboxyethylrhodanine, 3p-'carboxyphenylrhodanine, 3-carboxymethyl 2 thio-'2,4- (3,5)oxazoledione, 1-methyl-3-p-sulfophenyl-5- pyrazolone, 1,3-dipheny1 2 thiohydantoin, 1- ethyl 3 phenyl 2 thiohydantoin, l-carboxymethyl-3-phenyl-2-thiohydantoin, 3-B-sulfoethylrhodanine, etc.

The hydroxy cyclammonium alkohalides can be condensed with heterocyclic compounds contain ing, substituted on the methylene group, an acyl ated arylaminomethylene group, e. g. 5-acetani- 5-acetanilidomethyl-.

lidomethylenerhodanines, ene-2-thiohydantoins, 5-acetanilidomethylene-2- thio2,4(3,5)-oxazolediones, etc., in the presence of a basic condensing agent, e. g, the tertiary amines set forth above.

The hydroxy cyclammonium alirohalides can be condensed with dialkylaminobenzaldehydes, e. g. p-dimethylaminobenzaldehyde, p-diethylaminobenzaldehyde, etc. to give styryl dyes. densations are advantageously carried out in the presence of a secondary amine, e. g. piperidina methylpiperidines, etc.

The hydroxy cyclammonium alkohalides can be styryl dyes sensitize photographic silver halide" emulsions, especially the customarily employed gelatino-silver-chloride, chlorobromide, chlorobromoiodide, bromide and bromoiodide emulsions, when incorporated therein, e. g. in a concentration of from 10 to 40 mg. per liter of emulsion. The dyes can be added to the emulsions from The" The contheir solutions in methyl alcohol. The pyrrolo'e cyanine dyes described herein can be employed for the preparation of overcoating layers, filter layers and anti-halation layers for photographic elements.

Among the dyes that have been prepared from the hereindescribed hydroxy cyclammonium quaternary salts are:

6,6'-dihydroxy 3,3 dimethylthiacarbocyanine iodide, fine dark green crystals, P. 331-332 C, with decomposition. V

3;3'-diethyl-.3,3' dihydroxythiacarbocyanine iodide, dark blue-green needles, M. .P. 2942 9 5 C. with decomposition.

9-ethyl-6,6' dihydroxy 3,3 dimethylthiacar bocyanine iodide, fine red needles, M. P. 30.7 308 C. with decomposition.

5 hy rxy 3.3 imethylth acerb oy mn iodide, MLP. 315-317 C. with decomposition. 3,3 .diethyl 5,5 dihydroxythiac'arbocyamne iodide, very dark needles, M. P. 333-335l C. with decomposition, 3,3'-diethyl -'5,'5' dihydroxy-Q methylthiacarbocyanine iodide, blue crystals, M. P, 313-314" C. with decomposition. 3,,3'-diethyl 5 ,5 dihydroxythiatrioarbocyanine iodide, fine, very dark crystals, M. P.,249-25 1 .C. with decomposition. 3.3 7 diethyl 5 hydroxyoxathiacarbocyanine iodide, steel blue needles, M. P. .29329.4 C. with decomposition. 3-ethyl 5.- '[(3 ethyl 5fhydroXy-2(3.) -benzothiazolylidenel'isopropylidenel 2 .thio 2,4-

'(3,'5')-oxazoledione, fine red needles, M. P. 273

lto274 C. with decomposition.

5 -"[(3 ethyl 5 hydroxybenzothiazolylidene).-

ethylidene] -3-ethylrhodanine,greenish crystals with a bright reflex, M. P. 304 to 305 C. with decomposition.

1-ethyl 5 hydroxy 3 methylthiae2' cyanine iodide, green crystals, M. P. 271-273 C. with decomposition.

2-p-dimethylaminostyryl 5 hydroxybenzothi- ,azole ethiodide,M. ,P. 295=-296 C. with decomposition.

3-,ethyl+5-ihydroxy 2,5' dimeth l 1' phenyloxapyrrolocarbocyanine iodide, ,P. 27.3 to 2l4';C.-with decomposition.

What we claim as our invention and desire to.

wherein Q represents an atom selected; from; the groupconsistingof an oxygen-atom, a sulfur atom and a-selenium atom, and -R and;R1 each represents an alkyl group.

8 2. A process for preparing a hydroxy-benzoe thiazole quaternary salt comprising hy.drolyz-.- ing at a temperature of from to C., in the presence of hydrobromic acid, an alkoxybenzothiazo-le alkiodide selected from the group con sisting of those represented by the following eneral formula:

wherein R represents an alkyl group of the forthe group consisting of those represented by the.

following general formula:

wherein R represents an alkyl group of the --formulaCnH2n+1 wherein n represents a positive integer of from .1 to 2 and R1 represents .a primary alkylgroupcontaining from 1 to 4 carbon atoms.

A. Aprocessrfor preparinga hydroxybenzothiazole quaternary. salt comprising hydrolyzing at atemperatureof from 80 to 150 C., in-the pres,- ence of constr int boiling hydrobromic acid, .5- m ethoxy-2 inethylbenzothiazole ethiodide.

,5.. ,A-proc es s for preparing a hydroxybenzothi o e ua erna s t c pri n ely ingat a temperature offrom 80--to 150 C.,in t h e presence of constantiboiling hydrobrornicacid, 6 inethoxy-2-methylbenzothiazole ethiodide.

6. A, pr0cess for preparing a hydroxybenzoxazole quaternary salt comprising hydrolyzing at a ternperature of froml80 to 150 0., in the presence ,of constant .boiling hydrobromic .acid, 5,-

methogry- Z-nrethylloenzoxaaqle ethiodide.

-EARL J. VAN LARE.

LESLIE G. S. BROOKER.

REFERENCES CITED "The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Chemical-Ab tract 4 3 7e tin i'pri nov. J1

Gen. Chem. (USSR), vol. 15, pp. 200-206. 

1. A PROCESS FOR PREPARING A HYDROXY CYCLAMMONIUM QUATERNARY SALT COMPRISING HYDROLYZING AT A TEMPERATURE OF FROM 80* TO 150* C., IN THE PRESENCE OF HYDROBROMIC ACID, AN ALKOXY CYCLAMMONIUM ALKIODIDE SELECTED FROM THE GROUP CONSISTING OF THOSE REPRESENTED BY THE FOLLOWING GENERAL FORMULA: 